Lenvatinib-Induced Destructive Thyroiditis in a Patient With Hepatocellular Carcinoma

Lenvatinib is an antineoplastic oral agent that acts as a multi-kinase inhibitor against vascular endothelial growth factor (VEGF). This drug is commonly known for its use against radioiodine-refractory differentiated thyroid cancer, but it is also approved for unresectable hepatocellular carcinoma (HCC). Side effects such as fatigue, hypertension, palmar-plantar erythrodysesthesia, diarrhea, decreased appetite, and hypothyroidism are frequently reported adverse effects. However, the incidence of hyperthyroidism is a less known phenomenon. This case describes a patient with HCC on lenvatinib therapy who develops destructive thyroiditis. A 69-year-old man with hepatitis c cirrhosis complicated by progressive hepatocellular carcinoma (Child-Pugh class A6) presented with generalized weakness, unintentional weight loss, heat intolerance, palpitations, and tremors. He had been started on chemotherapy with lenvatinib 12 mg/day four weeks prior to presentation. Endocrinology was consulted due to abnormal thyroid function tests (TFTs). He had no previous history of thyroid function abnormalities or family history of thyroid disease. Laboratory tests revealed a hyperthyroid state [total thyroxine (T4), 14.3 µg/dL (normal range 4.5-11.7); free thyroxine (FT4), 1.9 ng/dL (normal range 0.9-1.7); thyroid-stimulating hormone (TSH), 0.07 µIU/mL (normal range 0.27-4.20), and negativity for antibodies [anti-thyroid peroxidase antibody (TPO Ab), 0.8 IU/mL (normal range 0.0-9.0); thyroglobulin antibody (Tg Ab), < 0.9 IU/mL (normal range 0.0-4.0); thyroid stimulating immunoglobulin (TSI), 90% (normal range < 122)]. Ultrasonography revealed a mildly prominent thyroid gland, a homogenous echo texture, and no suspicious thyroid nodules. In addition, a 99m-technetium (99mTc) scintigraphy demonstrated reduced radioactive uptake that was consistent with thyroiditis. Therefore, this patient was diagnosed with lenvatinib-induced destructive thyroiditis. Palpitations improved with a beta-blocker and the patient was resumed on a lower dose of lenvatinib, 8 mg/day, one week later. About six weeks after the initial dose of lenvatinib, his TFT results normalized. Lenvatinib disrupts cell proliferation which can affect many organs, including the thyroid gland. Although several theories have been proposed, the exact underlying mechanism by which this occurs remains unknown. It is important to note that in addition to hypothyroidism, lenvatinib may also cause hyperthyroidism in the form of a transient destructive thyroiditis. This emphasizes the need to routinely check TFTs prior to the initiation of lenvatinib and throughout the course of therapy.